Tumors of the Salivary Glands

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32 Tumors of the Salivary Glands

Malignant salivary gland tumors are uncommon head and neck cancers. They share many characteristics, yet also have features that are uniquely attributable to their respective locations and subtypes. The two main categories are major and minor salivary gland tumors. They are presented separately to distinguish the presentations, natural histories, and therapeutic approaches between and within these groups.

Major Salivary Gland Tumors

Epidemiology

Tumors of the major salivary glands are uncommon and account for approximately 2% to 7% of all head and neck neoplasms. In adults, the annual incidence is approximately one to four new cases per 100,000 individuals. The parotid gland is overwhelmingly the most frequent gland affected; cancer in the parotid gland is much more common than submandibular and sublingual gland cancers by a factor of 10 and 100, respectively.

The ratio of benign to malignant tumors varies by site, and there is an inverse relationship between the size of the salivary gland and its incidence of malignancy: (1) parotid gland: 80% benign (primarily pleomorphic adenomas), 20% malignant; (2) submandibular gland: 50% benign, 50% malignant; (3) sublingual gland: less than 40% benign, more than 60% malignant. The average age for benign neoplasms is 40 years, whereas that for malignant tumors is 55 years. The incidence is equivalent for men and women.

The causal factors of these malignant tumors is unknown. The usual risk factors for squamous cell carcinomas of the head and neck—excessive use of tobacco and alcohol—are not clearly proven causal agents for malignant salivary gland tumors. Radiation-induced salivary gland malignancies have been reported in the literature in association with patients who had been irradiated to the head and neck region for benign conditions (e.g., acne, tinea capitis, infected tonsils) and in survivors of the atomic bomb in Hiroshima and Nagasaki. Although an association with female breast cancer has been reported, there is a lack of firm epidemiologic data to support this contention. Nutritional deficiency as a possible cause has been reported in the Arctic Inuit peoples who have a diet low in vitamins A and C. Infection has been cited as a possible cause in whites with the Epstein-Barr virus. Other possible epidemiologic causes include alcohol use, hair dye, and a higher education level.

Anatomy

The major salivary glands comprise the parotid, submandibular, and sublingual salivary glands (Fig. 32-1). Each are paired glands that have different secretory functions: (1) parotid gland—serous; (2) submandibular gland—seromucous; (3) sublingual gland—mucous.

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FIGURE 32-1 • The anatomic locations of major salivary glands: parotid, submandibular, sublingual.

(From Spiro JD, Spiro RM: Salivary tumors. In Shah J (ed): Cancer of the head and neck, London, 2001, BC Decker, p 241.)

Parotid Gland

The parotid glands are the largest of the salivary glands (see Fig. 32-1 and Fig. 32-2). These paired glands are surrounded by a discrete capsule and have the following anatomic landmarks: (1) anterior—wraps around the ascending mandibular ramus anterior to the tragus and extends toward the anterior margin of the masseter muscle; (2) posterior—extends from the angle of the mandible under the earlobe toward the mastoid tip; (3) superior—extends to the inferior aspect of the zygoma at the temporomandibular joint level; (4) inferior—extends to the inferior aspect of the angle of the mandible; (5) medial—borders the parapharyngeal-base of skull; (6) lateral—located below the skin of the preauricular cheek–upper neck. The gland is divided into two lobes by the path of the facial nerve, which exits from the stylomastoid foramen (Fig. 32-3): (1) superficial lobe—accounts for 80% of the gland and is located just lateral to the facial nerve; (2) deep lobe—accounts for 20% of the gland and is located medial to the facial nerve and adjacent to the medial aspect of the angle of the mandible and is connected to the superficial lobe by the isthmus (Fig. 32-4). The deep lobe is in close anatomic proximity to the internal carotid artery; the internal jugular vein; the cervical sympathetic chain; and the cranial nerves IX, X, XI, and XII (Table 32-1).

image image

FIGURE 32-3 • A, Pathway of the facial nerve (cranial nerve VII) as it exits the stylomastoid foramen and then branches out into various anatomic regions. B, Note the presence of the deep lobe of the parotid gland just medial to the facial nerve. C, The facial nerve branches have several distribution variations.

(A from Leblanc A: The cranial nerves, ed 2, Berlin, 1995, Springer-Verlag, p 184. B from Crumley RL, Kelley TF: Rehabilitation of the patient with tumors of the salivary glands. In Thawley SE, Panje WR, Batsakis JG, et al (eds): Comprehensive management of head and neck tumor, vol 2, Philadelphia, 1987, WB Saunders, p 1202. C from Som PM, Curtin HD: Head and neck imaging, ed 3, St Louis, 1996, Mosby, p 829.)

Table 32-1 The Anatomic Relationship of the Major Salivary Glands and Cranial Nerves

Major Salivary Gland Adjacent Cranial Nerve Base of Skull Foramen
Parotid    
Superficial/deep lobes Facial nerve (CN VII) Stylomastoid foramen
Deep lobe Glossopharyngeal nerve (CN IX) Jugular foramen
  Vagus nerve (CN X) Jugular foramen
  Accessory nerve (CN XI) Jugular foramen
  Hypoglossal nerve (CN XII) Hypoglossal canal
Submandibular Lingual nerve (CNV3) Foramen ovale
  Facial nerve (CN VII): Stylomastoid foramen
  Mandibular/cervical branches  
  Hypoglossal nerve (CN XII) Hypoglossal canal
Sublingual Lingual nerve (CN V3) Foramen ovale

CN, Cranial nerve.

The parotid gland drains into the oral cavity through the Stensen duct (Fig. 32-5). This duct runs from the upper anterior third of the parotid gland and exits through the buccal mucosa by the second molar. The lymphatic drainage of the parotid gland progresses in an orderly fashion. Initially, it drains into the periparotid (Fig. 32-6) and intraparotid (Fig. 32-7) nodes that comprise two groups located within the fascia of the gland in two respective locations: between the gland and the superficial fascia and within the parenchyma. It then drains into the submandibular nodes (level IB), the upper (level II) and mid (level III) cervical nodes, and sometimes to the retropharyngeal nodes. Drainage to the contralateral nodes is very rare. However, it must be considered if the primary tumor extends across the midline or if there is massive ipsilateral cervical node involvement, which may disrupt the lymphatic pathways and cause spread to the opposite side.

image

FIGURE 32-6 • Periparotid lymph nodes are located on the surface of the superficial lobe but within the fascia.

(From Hoffman H, Funk G, Endres D: Evaluation and surgical treatment of tumors of the salivary glands. In Thawley SE, Panje WR, Batsakis JG, et al (eds): Comprehensive management of head and neck tumors, vol 2, Philadelphia, 1987, WB Saunders, p 1112.)

image

FIGURE 32-7 • Intraparotid nodes are located within the parenchyma of the gland.

(From Hoffman H, Funk G, Endres D: Evaluation and surgical treatment of tumors of the salivary glands. In Thawley SE, Panje WR, Batsakis JG, et al (eds): Comprehensive management of head and neck tumors, vol 2, Philadelphia, 1987, WB Saunders, p 1112.)

Adjacent to the superficial surface of the parotid gland fascia and anterior to the tragus are the preauricular nodes, which measure less than 3 mm in size and lie within the subcutaneous fat. These lymph nodes receive the lymphatic drainage from the dermis of the upper face, temple of the scalp, eye, nose, and ear. Their involvement is usually associated with skin carcinomas and melanomas in these regions as well as lymphomas. However, primary parotid malignancies do not commonly metastasize to these nodes. Secondary extension into the parotid gland and adjacent facial nerve can sometimes occur. These nodes can then drain into either the inferior parotid nodes (superficial lymph nodes) or into the jugular chain of nodes (level II).

Occasionally, there is an accessory parotid lobe (Fig. 32-8). This lobe has been reported in 21% of normal adult cadavers.1 However, in a review of 2261 patients with parotid lesions at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1939 and 1978, only 23 patients (1%) had an accessory parotid gland.2 Accessory parotid glands are located either cephalad or lateral to the anterior aspect of the Stensen duct and lie over the anterior aspect of the masseter muscle but are separate from the superficial lobe of the parotid gland. Clinically, they are adjacent to the Stensen duct, which is located midway along a line drawn between the tragus of the ear to the lateral upper lip. There can be 1 to 10 tributary ducts from the accessory lobe that will empty into the Stensen duct. This lobe can be clinically significant in that it may be the primary site of a malignant tumor that presents as an asymptomatic swelling in the mid cheek region.

image

FIGURE 32-8 • A, The accessory parotid lobe is located in the anterior aspect of the Stensen duct. B, Normal parotid gland and the Stensen duct.

(From Johnson FE, Spiro RH: Tumors arising in accessory parotid tissue, Am J Surg 138:242, 1979.)

Submandibular Gland

The submandibular gland (see Fig. 32-1) is 25% of the size of the parotid gland and measures 3 to 4 cm. These paired glands are surrounded by a capsule and are located in the upper anterior triangle of the neck. They are medial to the proximal half of the mandible (Fig. 32-9). The majority of the gland is over the external surface of the mylohyoid muscle, which forms the muscular floor of mouth in the region between the insertion of the muscle and the mandible and which divides the gland into contiguous superficial and deep portions (Fig. 32-10). The posterior aspect is anterior to but near the lower anterior margin of the parotid gland. The inferior aspect can extend caudad a fair distance and approaches the level of the hyoid bone. Of clinical importance is the fact that the submandibular gland is lateral to and abuts the lingual nerve (cranial nerve V3) and hypoglossal nerve (cranial nerve XII) and is medial to the marginal mandibular and cervical branches of the facial nerve (cranial nerve VII) (see Table 32-1).

image

FIGURE 32-10 • Anatomic relationships between the submandibular gland and sublingual gland and the adjacent musculature and cranial nerves.

(A and B from Spiro JD, Spiro RM: Salivary tumors. In Shah J (ed): Cancer of the head and neck, London, 2001, BC Decker, p 241.)

The glands drain into the oral cavity through the Wharton duct. This 5-cm duct courses through the niche between the mylohyoid and hypoglossus muscles and emerges in the anterior floor of the mouth toward the midline.

The lymphatic drainage of the submandibular glands progresses in an orderly fashion. Initially it drains into the adjacent submandibular nodes (level IB) as there are no intraglandular parenchymal nodes. It then drains into the upper (level II) and mid (level III) cervical nodes. Drainage to the contralateral nodes is rare.

Sublingual Gland

The paired sublingual salivary glands (see Fig. 32-1) are the smallest of the major salivary glands and are approximately 10% of the size of parotid glands. These glands do not have a discrete capsule. They are located in the anterior floor of mouth adjacent to the medial aspect of the mandible and occupy a submucosal position. Sublingual salivary glands are adjacent and superior to the mylohyoid muscle in the area of the sublingual depression. They occupy a position just medial to the inner surface of the mandible near the mental symphysis (see Fig. 32-10). It is clinically important to note that the lingual nerve (cranial nerve V3) courses adjacent to the sublingual gland (see Table 32-1).

Primary malignant tumors of the sublingual glands are rare; however, any lesion in this area must be considered malignant until proven otherwise. It may be difficult to clinically rule out a primary squamous cell carcinoma of the anterior floor of mouth in this region.

These salivary glands drain into the oral cavity via 5 to 15 ducts (Rivinus ducts) that empty into the sublingual fold of the floor of mouth. Also, these ducts may anastomose to create a larger duct known as the Bartholin duct, which attaches to the submandibular duct.

The lymphatic drainage of the sublingual glands progresses in a predictable, orderly fashion, flowing initially to the submental (level IA) and submandibular nodes (level IB) and then to the deep jugular nodes (level II).

Pathologic Conditions

Malignant Tumors

Histopathologic Types

During the past several years, the World Health Organization has expanded its list of suggested histopathologic typing to include a very comprehensive and varied group of malignant tumors:

The relative incidence of the different histologic types according to gland of origin is detailed in Table 32-2.

Table 32-2 Distribution of Histologic Types of Major Salivary Gland Cancer

Type Percentage
Parotid (n = 1778 cases)  
Mucoepidermoid 32
Adenocarcinoma 16
Malignant mixed 14
Adenoid cystic 11
Acinic 11
Undifferentiated and squamous 16
Submandibular (n = 383 cases)  
Adenoid cystic 41
Acinic 17
Mucoepidermoid 12
Malignant mixed 10
Undifferentiated 9
Squamous 9
Adenocarcinoma 2

Data from Memorial Sloan-Kettering Cancer Center.1

Adenoid Cystic Carcinoma

This is the predominant malignant histologic type in submandibular and minor salivary gland tumors.3 The appearance (Fig. 32-12) can vary from a cribriform pattern (differentiated) to a mixed cribriform pattern and solid features (moderately differentiated) to solid features (undifferentiated). Some authors have observed that the solid variety can have a more malignant behavior. The natural history can be varied, ranging from a matter of months to 20 years or more. The first evidence of recurrence can be 20 years after diagnosis, making it very difficult to ever determine that an individual patient is cured. Lymph node spread is distinctly uncommon (<5%). Adenoid cystic tumors can cause perineural spread, which may track along the pathways of the cranial nerves to the base of skull. This is important in planning radiation treatment. Many patients (ultimately up to 40%) will develop pulmonary metastases. Because prolonged survival can occur (10 to 20 years) with pulmonary metastases, the primary site must be managed adequately despite the presence of metastatic disease. An example of the management of the primary site in a patient with adenoid cystic cancer and lung metastases is illustrated in Fig. 32-13.

Histologic Grade

The histologic grade or cellular differentiation of the tumor is one of several important factors affecting patient survival. The other indicators include the histologic diagnosis, site, size, degree of fixation, or local extension and facial nerve involvement. Also, regional lymph node and distant metastases are of major importance relating to survival. However, the histologic grade of the tumor is applicable only for adenocarcinoma not otherwise specified and mucoepidermoid carcinomas, or when either of these is the malignant component of carcinoma in pleomorphic adenoma. For all of the other subtypes, it is the actual histologic type that defines the grade. For instance, salivary duct carcinoma is high-grade whereas basal cell adenocarcinoma is low-grade by definition.

Clinical Presentation and Evaluation

Parotid

Primary Site

A thorough history and carefully detailed physical examination are always crucial first steps in the evaluation of patients with a parotid mass. The differential diagnoses of a parotid mass include a malignant tumor as well as several types of benign causes (Table 32-3). Parotid malignancy is usually an asymptomatic mass. However, as the lesion progresses and enlarges, episodic pain occurs in 10% to 20% of cases; subsequently, significant pain can result and become constant. Patients can present with complaints of an inability to move one side of the face (cranial nerve VII), a shoulder (cranial nerve IX), or one side of the tongue (cranial nerve XII) as the adjacent cranial nerves become involved by the malignant tumor. Clinical presentations can vary according to the histopathologic findings (Table 32-4).

A careful and methodic examination of the patient can provide valuable information regarding the stage of the tumor. The mandibular opening should be measured to rule out trismus resulting from tumor involvement of the pterygoid plates. Bimanual palpation of the tumor will provide data regarding its dimensions, texture, and mobility. The overlying soft tissues, adjacent mandible, and ipsilateral external auditory canal are sites where tumors can infiltrate and should be carefully evaluated.

The functional status of the adjacent cranial nerves must be documented. This always includes evaluation of the facial nerve (cranial nerve VII), which is involved in 2% to 14% of cases. However, if the deep lobe of the parotid is involved, cranial nerves IX, X, XI, and XII may be affected.

Workup with computed tomography (CT) or magnetic resonance imaging (MRI) can be helpful in selected cases. Slices should cover from above the ears to below the clavicles, thus imaging the base of skull, parotid, retropharyngeal nodes, cervical nodes, and supraclavicular nodes. There are four indications for a pretreatment CT or MRI in parotid gland tumors4: (1) deep lobe parotid tumors, (2) neurologically symptomatic tumors, (3) recurrent tumors, and (4) large tumors.

CT and MRI cannot differentiate a benign from a malignant tumor and thus are not routinely used for small, mobile, circumscribed lesions. An MRI scan with gadolinium best delineates deep-tissue infiltration or perineural extent of the tumor with respect to the facial nerve (cranial VII).

Both benign and malignant salivary tumors may appear well circumscribed on CT or MRI. This may cause one to underestimate the actual extent of infiltration of the cancer.

In the initial evaluation of salivary gland tumors, 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scans must be judiciously employed. The salivary gland takes up FDG from the blood and subsequently excretes it in the saliva. There is normal variability in the degree of such uptake, however. Parotid and submandibular glands generally have a mild to moderate degree of physiologic FDG uptake. Salivary gland tumors, whether benign or malignant, may or may not show a significant uptake of FDG. Tumors with low metabolic activity may be associated with minimal or no uptake; this increases the risk for a false-negative result. Benign (e.g., Warthin tumor, pleomorphic adenoma) and malignant (e.g., primary parotid lymphoma) parotid tumors with uptake are indistinguishable and may give rise to a high false-positive rate. Also, a malignancy may cause bilateral FDG uptake in parotid or submandibular glands, which can mimic a normal physiologic pattern. There are some salivary gland malignancies that have little or no FDG uptake. The use of a PET scan in the preoperative setting has not been useful. However, once a histologic diagnosis has been made establishing a malignancy of a salivary gland, a PET scan may of be helpful for evaluation of distant metastasis. In general, one can consider using a PET scan in high-grade salivary gland malignancies.

The initial diagnostic procedure in a patient suspected of having a parotid gland malignancy can be a fine-needle aspiration (FNA) biopsy. This is a safe technique that is not associated with tumor spread along the fine-gauge needle tract, which can occur with large-bore needles.

The harvested cells allow for cytopathologic diagnosis based on the appearance of individual cells and cell clusters. It is important to note, however, that such a limited sampling of cells may not provide an accurate analysis of the full morphologic spectrum and this can be associated with major difficulties in cytologic diagnosis. Different salivary tumors that are both clinically and biologically different may appear quite similar on a cellular evaluation. Also, some malignant salivary tumors microscopically do not look frankly malignant.

In general, 75% to 80% of parotid masses are benign and 20% to 25% are malignant. An FNA biopsy is an accurate diagnostic technique with overall sensitivities of greater than 90% and specificities of greater than 95%.510 FNA biopsies are as accurate as frozen section analysis in parotid masses. Note that a malignant salivary gland tumor is more likely to be inaccurately diagnosed as a benign lesion than an adenoma is to be erroneously called a malignant lesion. Salivary gland lesions that are particularly associated with difficulties in achieving an accurate diagnosis include acinic cell carcinomas (false-negative confusion for a benign process), monomorphic adenomas (false-positive confusion with an adenoid cystic carcinoma), and lymphoid lesions (both false-negative and false-positive diagnoses).

If a malignancy is thus diagnosed, one can assess if it is a primary parotid lesion or if it is a metastatic lesion to the parotid gland from another primary site. In the former situation, appropriate radiographic evaluation and surgical planning can occur and important discussions can be held with the patient. For metastatic lesions to the parotid gland from another primary site, appropriate workup can be initiated to determine the anatomic origin. The most frequent primary malignant sites include skin areas with lymphatic drainage to the parotid gland lymph nodes (80%), the thyroid gland, kidney, and breast.

It should be noted that the routine use of an FNA biopsy in this fashion is controversial because some surgeons believe that it would not change their standard approach, a parotidectomy, and thus would add little to the management of such tumors. Some institutions reserve the FNA biopsy for inoperable or recurrent lesions. However, incisional or excisional biopsies are never performed to establish a tissue diagnosis because such procedures can increase the likelihood of recurrence, the risk of injury to the facial nerve, and subsequent surgical morbidity (because a wide removal of the biopsy site must then be added to the cancer surgery).

Lymph Nodes

Although the overall risk (18%)11 of lymphatic spread is less common than for mucosal squamous cell carcinomas of the head and neck, it is still essential to carefully evaluate the regional lymph nodes. The influence of tumor histologic features on the frequency of clinically involved nodes at presentation in 474 previously untreated major salivary gland cancers was reviewed by Armstrong from MSKCC.12 These data are presented in Table 32-5. The risk of nodal involvement increases with grade and size. However, adenoid cystic cancer, despite often being aggressive histologically and large in size, had only a 2% rate of clinically evident metastases.

Table 32-5 Clinically Involved Nodes at Presentation in Major Salivary Gland Cancers: The Influence of Tumor Histology

Histologic Subtypes Number (%)
Anaplastic 6/7 (86)
Epidermoid 6/28 (21)
Adenocarcinoma 11/49 (22)
Mucoepidermoid 30/209 (14)
Malignant mixed 11/69 (16)
Acinic 2/55 (2)
Adenoid cystic 1/55 (2)
Oncocytoma 0/2 (0)
Total 67/474 (14)

Data from Armstrong et al.12

In the series reported by Armstrong and associates,12 overall clinically occult, pathologically positive nodes occurred in 12% (47/407). By univariate analysis, several factors appeared to predict the risk of occult metastases, but multivariate analysis revealed that only size and grade were significant risk factors. Tumors of 4 cm or more had a 20% (32/164) risk of occult metastases, compared with a 4% (9/220) risk for smaller tumors (P < 0.00001). High-grade tumors (regardless of histologic type) had a 49% (29/59) risk of occult metastases, compared with a 7% (15/221) risk for intermediate or low-grade tumors (P < 0.00001). The effects of tumor histologic anatomy and grade on occult nodal metastases are detailed in Tables 32-6 and 32-7.

Table 32-6 Effect of Tumor Histology on Occult Lymph Node Involvement in Major Salivary Gland Cancers

Histologic Subtypes Number (%)
Epidermoid 9/22 (41)
Adenocarcinoma 7/38 (18)
Mucoepidermoid 26/179 (14)
Acinic 2/53 (4)
Adenoid cystic 2/54 (4)
Anaplastic 1/1  
Malignant mixed 0/58  
Oncocytoma 0/2  
Total 47/407 (12)

Data from Armstrong et al.12

Table 32-7 Effect of Tumor Grade on Occult Lymph Node Involvement in Major Salivary Gland Cancer

Tumor Grade Number (%)
Low 2/125 (2)
Intermediate 13/96 (14)
High 29/59 (49)

Data from Armstrong et al.12

It is rare for a low-grade tumor to metastasize to the regional nodes. All high-grade lesions carry a significant risk for nodal metastasis irrespective of the histologic type. High–T stage lesions are associated with an increased incidence of nodal metastasis. Submandibular or sublingual primary salivary malignancies have an increased risk for nodal spread compared with parotid salivary malignancies. The histologic type can influence the risk for nodal metastasis as well. Mucoepidermoid carcinoma, squamous cell carcinoma, and undifferentiated carcinoma are associated with a high incidence of nodal metastasis; however, adenoid cystic carcinoma, malignant mixed carcinoma, and acinic cell carcinoma have a low incidence (see Tables 32-5 and 32-6).

The physical examination includes palpation of the preauricular-parotid region (preauricular, intraparotid, and periparotid nodes); submandibular nodes (level IB); upper cervical nodes, especially the superior deep jugular nodes and jugulodigastric nodes (level II); and mid cervical nodes (level III). The ipsilateral tonsillar region should be inspected for fullness, which may indicate gross retropharyngeal nodal involvement, particularly when the deep lobe of the parotid is infiltrated by tumor. Any adenopathy is documented by location, size, number, texture, tenderness, and mobility. The initial radiographic evaluation of the parotid gland may also provide important clinical information regarding the nodal status.

Submandibular Gland

Primary Site

A submandibular salivary gland tumor usually presents as an asymptomatic mass but can be associated with episodic pain in 6% to 7% of cases. However, as the lesion progresses and enlarges, significant pain can develop and become constant. Patients can infrequently present with complaints of decreased sensation in the ipsilateral lower teeth, gums, and lower lip (cranial nerve V3); an inability to move the ipsilateral oral tongue (cranial nerve XII); or facial weakness associated with the marginal mandibular or cervical branch of the facial nerve (cranial VII) as the adjacent cranial nerves become involved with the malignant tumor (14%).

A careful and methodic examination of the patient can provide valuable information regarding the stage of the tumor. Bimanual palpation of the lateral floor of mouth area will provide data regarding tumor dimension, texture, and mobility. The overlying soft tissues and adjacent mandible are sites where tumors can infiltrate and should be carefully evaluated. The functional status of the adjacent cranial nerves must be documented. This includes the marginal mandibular or cervical branch of the facial nerve (cranial nerve VII) or both, the lingual nerve (cranial nerve V3), or the ipsilateral hypoglossal nerve (cranial nerve XII).

Submandibular gland tumors are seldom imaged because they usually present early and are easily palpated. Note that large primary parotid gland lesions can push down into the submandibular space, thus giving the erroneous clinical impression that there is enlargement of the submandibular gland. If this is suspected in a particular case, one must radiographically evaluate the parotid gland with a CT or MRI. An obstructing calculus within the Wharton duct can cause retrograde pressure and thus result in enlargement of the submandibular gland. Enlargement of upper cervical lymph nodes can displace the submandibular gland, thus forming a “pseudomass.”

Based on the particular characteristics of a submandibular tumor, an MRI scan may be indicated to assist in evaluating for deep-tissue infiltration or perineural extent of the tumor with respect to the lingual nerve (cranial nerve V3), the hypoglossal nerve (cranial XII), and the marginal mandibular and cervical branches of the facial nerve (cranial nerve VII).

CTs or MRIs cannot generally differentiate between a benign or malignant submandibular mass and thus are not routinely used for small, mobile, circumscribed tumors. However, these studies can determine whether the mass is within the submandibular gland or extrinsic to it (e.g., dermoid, neural lesion, ranula, thyroglossal duct cyst, lymph node). Both benign and malignant salivary tumors may appear well circumscribed on a CT or MRI. This may cause one to underestimate the actual extent of infiltration of the cancer.

Concerns regarding the use of an FDG PET scan are similar to those discussed previously for parotid salivary gland malignancies.

The initial biopsy of a suspicious submandibular salivary gland mass can be an FNA biopsy. Such a procedure is important because only a minority of submandibular masses are primary tumors originating in that gland. Note that, in general, a submandibular gland mass has a 50% chance of being malignant. An FNA biopsy is useful only if it reveals a malignancy. It is important to recognize that the mass may be an enlarged submandibular lymph node (level IB), and a careful evaluation of the head and neck for a primary mucosal lesion (e.g., oral cavity, maxillary antrum) must be performed. All suspicious lesions are approached surgically with a submandibular triangle dissection despite a negative FNA biopsy. Incisional or excisional biopsies are never performed to establish a tissue diagnosis because such procedures increase the probability of recurrence and the risk of surgical morbidity because a wide removal of the biopsy site must be added to the final definitive surgical procedure. The only exception to this rule is when there is a small tumor of the submandibular gland that is surrounded by normal parenchyma—then a simple excision of the submandibular gland may be performed.

Sublingual Salivary Gland

Primary Site

A sublingual salivary gland tumor usually presents as an asymptomatic swelling in the anterior floor of mouth. It may be difficult differentiating a primary lesion of the sublingual gland from a primary lesion of the floor of mouth. Up to 15% of patients with such a malignancy can have associated pain. Patients may complain of ipsilateral loss of tongue sensation (cranial nerve V3).

A careful and methodic examination of the patient can provide valuable information regarding the stage of the tumor. Bimanual palpation of the floor of the mouth will provide data regarding tumor dimension, texture, and mobility. Because adjacent soft tissues are sites where tumor can infiltrate, they must be carefully evaluated. The functional status of the ipsilateral lingual nerve (cranial nerve V3) must be documented.

Considerations regarding the use of CT, MRI, and FDG PET imaging are similar to those noted previously for submandibular salivary gland tumors.

The initial biopsy procedure of a suspicious sublingual region mass can be an FNA biopsy. Note that, in general, most sublingual salivary gland masses are malignant. Such a procedure is useful only if the biopsy reveals a malignancy. It is important to recognize that the mass may represent a primary minor salivary gland tumor in the anterior floor of mouth. These lesions, despite a negative FNA biopsy, should be resected with a formal cancer procedure. Incisional or excisional biopsies are never performed to establish a tissue diagnosis because such procedures increase the recurrence risk and the risk of surgical morbidity because a wide removal of the biopsy site must be added to the final definitive cancer surgery.

Staging

The American Joint Committee on Cancer (AJCC) has established the staging criteria for major salivary gland tumors. This system is based on an extensive retrospective review of the world’s literature.

The AJCC clinical staging is based on three major categories of evaluation: (1) history—pain, trismus, unilateral facial weakness; (2) clinical examination findings—size of mass, fixation, extension to adjacent tissues, involvement of adjacent cranial nerves; and (3) radiologic findings.

Several factors influence patient survival and are reflected in the AJCC staging criteria: histologic type, cellular differentiation of the tumor (grade), site, size, degree of fixation or local extension, facial nerve involvement, status of regional lymph nodes, status of distant metastasis.

Periodically, the staging criteria are reviewed and modified to better establish a system that reflects contemporary technology and therapeutic interventions. The current AJCC Cancer Staging Manual (Table 328) represents the seventh edition, published in 2010.14 The following examines the changes from the sixth edition (2002)15 as they relate to major salivary gland tumors.

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